Triethylamine → HCID 178452060, compound

HRID 424598Notes

Reaction equation

HRID 424598 reaction equation
[NH2:1][C:2]1[C:24]([F:25])=[CH:23][C:5]2[S:6][CH2:7][CH2:8][N:9]([CH:10]3[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]3)[C:4]=2[CH:3]=1.C(N(CC)CC)C.Cl.[S:34]1[CH:38]=[CH:37][CH:36]=[C:35]1[C:39](=[NH:42])OC>C(O)C.C(OCC)(=O)C>[F:25][C:24]1[C:2]([NH:1][C:39]([C:35]2[S:34][CH:38]=[CH:37][CH:36]=2)=[NH:42])=[CH:3][C:4]2[N:9]([CH:10]3[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[O:17])[CH2:12][CH2:11]3)[CH2:8][CH2:7][S:6][C:5]=2[CH:23]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 398426Methyl thiophene-2-carboximidate hydrochlorideHCID 59144114tert-Butyl 4-(6-amino-7-fluoro-2H-benzo[b][1,4]thiazin-4(3H)-yl)piperidine-1-carboxylate

Product 1

HCID 178452060HCID 178452060, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a stirred solution of tert-butyl 4-(6-amino-7-fluoro-2H-benzo[b][1,4]thiazin-4(3H)-yl)piperidine-1-carboxylate (168 mg, 0.457 mmol) in ethanol (5 mL) and triethylamine (0.643 mL, 4.57 mmol) was added methyl thiophene-2-carbimidate hydrochloride (325 mg, 1.829 mmol). The resulting mixture was stirred at 65° C. over the weekend. The mixture was then cooled to room temperature, diluted with ethyl acetate, and washed with saturated sodium carbonate (3×). The organic phase was dried, filtered, and concentrated, and chromatographed in 1:9 ethyl acetate:hexanes giving a yellow oil (18 mg, 8.26%); 1H NMR (MeOD-d4) δ 7.65-7.61 (m, 1H), 7.59-7.54 (m, 1H), 7.14-7.08 (m, 1H), 6.79 (d, J=10.5 Hz, 1H), 6.49 (d, J=7.5 Hz, 1H), 4.22-4.12 (m, 2H), 3.80-3.67 (m, 1H), 3.43-3.38 (m, 2H), 3.05-3.01 (m, 2H), 2.96-2.79 (m, 2H), 1.83-1.73 (m, 2H), 1.72-1.57 (m, 2H), 1.46 (s, 9H); ESI-MS (m/z, %): 477 (MH+, 100).

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. washwashed with saturated sodium carbonate (3×)
  3. customThe organic phase was dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customchromatographed in 1:9 ethyl acetate

Sources & evidence

ORD record
ord-ef1d113daa424feab6b52d563e7ae18d
Source dataset
uspto-grants-2012_01
Patent number
US08106043B2

Reaction notes

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